This is a renewal application for funds to support a broad-based Training Program on molecular-based research in disease-oriented neurobiology run by a 23 member, highly interactive Training Faculty with independent research funding and a long history of collaboration. Our major goal is to provide the scientific community with disease-trained neuroscientists familiar with state-of-the-art molecular approaches. These skills will range from the characterization and quantitative analysis of cellular products, to their molecular sequencing and genetic analysis. Emphasis will be placed on Alzheimer disease, AIDS encephalitis, multiple sclerosis, movement disorders and mechanisms underlying nervous system development. The Training Faculty comprises investigators mainly with neuropathology, neurology and neuroscience affiliations with interests encompassing basic and applied research into molecular mechanisms of disease, molecular neurobiology, immunology and cell biology. Also included will be cutting-edge approaches to questions of fundamental importance to neurologic disease, viz. glial cell lineage, transcriptional control of myelination, acquisition of neuronal phenotype and axon guidance. This program emanates from an institution renowned for the integration of cellular and molecular technologies to the study of neurologic disease and this tradition will be continued by a vibrant, multidisciplinary Training Faculty led by an investigator who has directed the program since its inception. The vibrant scientific atmosphere generated by this team is highly conducive for training in research. Predoctoral trainees (2 slots requested) with strong interests in molecular aspects of nervous system disease and development, will be recruited for admission into the Graduate Division of this institution. After coursework (1 year), trainees will join mentors'laboratories and will receive a PhD in either Pathology or Neuroscience in 4-5 years. Postdoctoral trainees (6 slots requested), will enter as MDs or PhDs and will be based in the mentor's laboratory, usually for a 2-3 year period. Trainees will be exposed to extensive seminar series on molecular neuropathology, molecular biology and cellular neuroscience and will emerge from the Program capable of generating independent research support and of translating the acquired technologies to the diagnosis, treatment and prevention of neurologic disease. This NRSA remains a major source of young investigators (clinical and basic), of diverse ethnicities, most of whom tend to remain in academia and assume leadership positions in disease-oriented molecular neuroscience.